Integrated Nanosecond Pulse Irreversible Electroporation (INSPIRE): Impact of Exposed Electrode Length on Ablation Geometry in an In Vivo Liver Model

Objectives: There is a critical need for effective focal therapies for patients with inoperable or anatomically complex tumors where conventional ablation techniques pose high risk or are ineffective. Integrated Nanosecond Pulsed Irreversible Electroporation (INSPIRE) is a novel non-thermal ablation modality which uses real time temperature feedback during pulse delivery to safely treat tumors near critical structures. This study evaluated the impact of exposed electrode length on ablation zone size, reproducibility, and cardiac safety in a large animal model.

Methods: INSPIRE treatments were performed in an in vivo healthy porcine liver model. All treatments administered 6000 V 1000 ns pulses with a 45 °C temperature set point. Treatments were administered percutaneously via an electrode and grounding pad approach using an internally cooled electrode applicator. The exposed electrode region at the distal end of the applicator was set to either 0.5, 1.0, 1.5, or 2.0 cm. Ablation zones were assessed via ultrasound, contrast-enhanced CT, and gross pathology one week post-treatment. Cardiac safety was evaluated by measuring pre- and post-treatment serum Troponin levels.

Results: All treatments were completed without adverse events. Troponin levels remained stable (pre: 0.249 ng/mL; post: 0.224 ng/mL), indicating no measurable cardiac injury. The 1.5 cm exposure length produced the largest and most consistent ablation volumes, with a mean volume of 12.8 ± 2.6 cm3 and average dimensions of 3.7 × 2.7 cm in under 6 min. Increasing exposure length beyond 1.5 cm introduced greater variability and reduced treatment volumes.

Conclusions: INSPIRE enables safe, large-volume, single-applicator ablation without a need for electrical pulse synchronization with R wave in cardiac rhythm. The 1.5 cm exposure length offers optimal balance between energy delivery and treatment consistency. These findings support further clinical investigation of INSPIRE for non-thermal ablation of inoperable tumors.

Simple Summary: Irreversible electroporation (IRE) is increasingly used to treat tumors in anatomically complex locations. However, clinical delivery can be challenging due to the potential for cardiac complications, intense muscle stimulation, and the need for multiple needle electrodes placed in parallel with precision under ultrasound guidance. This study evaluated INSPIRE, a next-generation IRE platform using bipolar pulse waveforms (1000 ns) and high-voltage (6000 V) pulses with real-time temperature control (45 °C). Using a simplified single-electrode and grounding pad approach, we found that a 1.5 cm electrode exposure length produced the most consistent and voluminous ablation zones (up to 12.8 cm3 in <6 min). Treatments were visualized well by contrast-enhanced CT and intraoperative ultrasound, and cardiac safety was confirmed by stable Troponin levels. These findings suggest that optimizing applicator geometry in INSPIRE can streamline workflow, enhance reproducibility, and expand safe access to non-thermal ablation in challenging clinical scenarios.